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World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies.

ABSTRACT: OBJECTIVE:To identify the prognostic biomarker candidates for stratification and long-term surveillance of oral leukoplakia progressing to cancer via a systematic literature review. MATERIALS AND METHODS:Systematic searches with no date restrictions were conducted on March 29, 2018, targeting the databases PubMed (Ovid), EMBASE (Ovid), EBM (Ovid), and Web of Science (ISI). Bias was assessed using the Quality in Prognosis Studies tool. Biomarkers were stratified based on hallmarks of cancer. RESULTS:Inclusion criteria were met by 25 of 3,415 studies. A range of biomarkers were evaluated experimentally for risk stratification, prognosis, and surveillance of oral leukoplakia in tissue, blood, and saliva. However, the studies were highly heterogeneous and require further validation. Biomarkers reported in these studies included inflammatory or oxidative markers, growth factors, ion channels, genetic and cellular regulatory factors, and epigenetic biomarkers. Studies tended to include small sample sizes, under-reported or variably reported histopathological data, did not address potential confounding, reported limited/variable follow-up data, or lacked a control group. Inclusion of subsets from chemoprevention trials may have introduced bias regarding reported malignant transformation rates and accuracy of prognostic biomarkers. CONCLUSIONS:This review identified insufficient longitudinal evidence to support validated prognostic biomarkers for oral leukoplakia. Further studies are needed to identify molecular targets with the potential to mitigate risk of malignant transformation.

SUBMITTER: Villa A

PROVIDER: S-EPMC6544170 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies.

Villa Alessandro A Celentano Antonio A Glurich Ingrid I Borgnakke Wenche S WS Jensen Siri Beier SB Peterson Douglas E DE Delli Konstantina K Ojeda David D Vissink Arjan A Farah Camile S CS

Oral diseases 20190601

<h4>Objective</h4>To identify the prognostic biomarker candidates for stratification and long-term surveillance of oral leukoplakia progressing to cancer via a systematic literature review.<h4>Materials and methods</h4>Systematic searches with no date restrictions were conducted on March 29, 2018, targeting the databases PubMed (Ovid), EMBASE (Ovid), EBM (Ovid), and Web of Science (ISI). Bias was assessed using the Quality in Prognosis Studies tool. Biomarkers were stratified based on hallmarks ...[more]

PMID: 31140698

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Project description:Oral leukoplakia (OL) is a potentially malignant oral disorder. The Gold Standard treatment is to remove surgically the OL. Despite optimal surgery, the recurrence rates are estimated to be 30%. The reason for this is unknown. The aim of this study was to investigate the clinical factors that correlate with recurrence after surgical removal of OL. In a prospective study data were collected from 226 patients with OL. Forty-six patients were excluded due to incomplete records or concomitant presence of other oral mucosal diseases. Overall, 180 patients proceeded to analysis (94 women and 86 men; mean age, 62 years; age range, 28-92 years). Clinical data, such as gender, diagnosis (homogeneous/non-homogeneous leukoplakia), location, size, tobacco and alcohol use, verified histopathological diagnosis, and clinical photograph, were obtained. In patients who were eligible for surgery, the OL was surgically removed with a margin. To establish recurrence, a healthy mucosa between the surgery and recurrence had to be confirmed in the records or clinical photographs. Statistical analysis was performed with the level of significance set at P<0.05. Of the 180 patients diagnosed with OL, 57% (N = 103) underwent surgical removal in toto. Recurrence was observed in 43 OL. The cumulative incidence of recurrence of OL was 45% after 4 years and 49% after 5 years. Fifty-six percent (N = 23) of the non-homogeneous type recurred. Among snuff-users 73% (N = 8) cases of OL recurred. A non-homogeneous type of OL and the use of snuff were significantly associated with recurrence after surgical excision (P = 0.021 and P = 0.003, respectively). Recurrence was also significantly associated with cancer transformation (P<0.001). No significant differences were found between recurrence and any of the following: dysplasia, site of lesion, size, multiple vs. solitary OL, gender, age, use of alcohol or smoking. In conclusion, clinical factors that predict recurrence of OL are non-homogeneous type and use of snuff.

Project description:Oral leukoplakia is the most prevalent potentially malignant disorder of the oral cavity. To evaluate its potential for malignancy, appropriate documentation of the biological parameters is crucial, allowing the patients' progression to be assessed. We hypothesized a lack of standardization in the parameters employed for the prognostic study of oral leukoplakia; our aims were to determine the different parameters used for follow-up according to definition, importance, and frequency of use, and to provide a standardization proposal of follow-up research. We made a scoping review to identify papers with the keywords "leukoplakia," "oral," and "follow-up" published until June 2019 in English, Spanish and Portuguese literature through an online search in PUBMED, SCIELO, and SCOPUS databases. In total, 514 articles were initially identified, and fifty-nine publications were selected, of which 37 were retrospective. The reports included a total of 18,660 patients between 13 and 98 years old, with a mean age of 57.6 years. Tobacco and alcohol habits were positive for 77 and 37% of the patients, respectively. Our results showed that reported leukoplakias were predominantly located on buccal mucosa (40.4%), were homogeneous (60.8%), multiple (59.9%), smaller than 2 cm (74.4%) and histopathologically non-dysplastic (71%). The mean follow-up time was 55 months, with a 13% malignant transformation rate. The categorization and definition of multiple variables were notably diverse. Age, sex, habits (tobacco and alcohol), site, size, distribution, morphology, degree of dysplasia, and evolution were the chosen parameters for our proposal. The current study reflected the lack of consensus found in the literature regarding parameters for diagnosis or follow-up, impacting negatively on clinical and research results. standardization comprises an efficient way to facilitate the prognosis assessment of oral leukoplakia, being beneficial for clinical practice, and enabling better quality information to apply in research.

Project description:ObjectiveOral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC.MethodThe Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset.ResultsWGCNA obtained the red module (r = -0.91, p < 0.05) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways (p < 0.05). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913-1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638-0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules.ConclusionsThis study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.

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World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies.

Publications

World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies.

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